Heart stimulation device

ABSTRACT

In the determination of an optimal rate for the delivery of stimulation pulses to a heart, the stroke volume (SV) of a heart ventricle is measured as a function of heart rate (HR), e.g. by determination of impedance in individual heart cycles whose duration is varied from the duration corresponding to the prevailing rate or the basic rate regarded as optimal for stimulation. The optimal rate should lie at the knee of this function. A corresponding knee is also found in the curve for cardiac output (CO). This rate is determined by calculation of an auxiliary function, e.g. HF=HR×CO, which displays a peak at the heart rate at which the knee is located, and the heart rate is determined which yields this maximum. The heart rate determined in this manner is subsequently employed as a basic rate.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to devices for determining the optimalrate for emission of a stimulation pulse to a heart.

2. Description of the Prior Art

The ability to control the heart rate by means of electrical stimulationis important to the well-being and survival of many people afflicted byvarious defects in the function of their hearts. Battery-poweredstimulation devices are available for different kinds of disorders.

The heart comprises a left atrium, right atrium, left ventricle andright ventricle and contains e.g. a sinus node (sinoatrial node. SAnode), an area made up of special tissue in the wall of the heart'sright atrium. In the normal, healthy state this area emits periodic,recurrent electrical pulses, each of which starting a heart cycle. Whenthe pulse from the sinus node is propagated across the walls of theatrium, it triggers contraction of the atrium for expulsion of bloodinto the corresponding ventricle. The pulse is carried to another tissuearea in the heart which has a special delay function, theatrioventricular (AV) node, from which it is carried on specialelectrically conductive tissue pathways to the ventricles. It is duringthis phase, when the electrical pulse passes along the conductivepathways to the ventricular walls, that blood is "pumped" from theatrium to ventricle. By the time this pulse arrives to triggercontraction of the ventricles, the ventricles have been expanded byinflowing blood and are ready to contract in order to pump blood to thelungs and circulatory system. After each contraction of the ventricles,a resting period starts during which the atria fill with blood, andlasts until the SA node generates the next pulse.

Normal rhythm, i.e. sinus rhythm, arises in the SA node. A faulty rhythmor rate, i.e. arrhythmia, can develop for different reasons. Forexample, the pathways, made of electrically conductive tissue, to or ina ventricle may be damaged or blocked so pulses emitted in the atriumare unable to trigger any contraction of the ventricle. In such cases,an electrical stimulation pulse can be supplied by an electronicstimulation device, i.e. a pacemaker. The generating of stimulationpulses by most of the stimulation devices currently in use issynchronized with or generally dependent on the heart's intrinsicelectrical activity. This activity can be monitored with sensorelectrodes placed somewhere in the patient's body, e.g. in or adjacentto the heart.

These sensor electrodes in an appropriate system sense electricalvoltages generated during heart activity. The electrical voltage sensedwith surface electrodes on the exterior of the body has the followinggeneral morphology during a heart cycle: A low voltage pulse, the Pwave, designates an atrial event, corresponding to depolarization ofmuscle cells in the walls of the atria, causing these walls to contract.A more complex pulse segment is referred to as the QRS complex andencompasses e.g. a large electrical pulse. This area designates aventricular event in the form of depolarization of muscle cells inventricular walls when these cells contract, and the heart's actualblood-pumping process is started and performed. A low voltage pulsefurther designates the start of repolarization of the cells inventricular walls, i.e. recovery from their preceding contraction, andis referred to as the T wave. These pulses/pulse segments normallyfollow each other over time, i.e. a P wave starts first in a heartcycle, followed by the QRS complex and, finally, the T wave. Thesesegments are not always distinguishable in the electrical voltage sensedby sensor electrodes placed in or by the heart. Thus, no T wave andoften not even the QRS complex are discernible with an electrode placedin an atrium. The P wave is not visible with an electrode in theventricle.

A typical stimulation device can operate in the following generalmanner: The stimulation device awaits an atrial event, signaled bycorresponding electrical activity in the heart, i.e. in practice theaforesaid P wave. If no P wave is detected within a first period of time(an atrial escape period), a stimulation pulse is sent to the atrium ofthe heart, stimulating muscle cells in atrial walls and causing them tocontract. A ventricular event is then awaited, i.e. the device analyzesthe voltage signal from the heart with respect to the presence of a QRScomplex. If no such complex is detected within a second period of time(a ventricular escape interval), a stimulation pulse is sent to theventricle, whereupon electrical activity in the atrium is again awaited.The interval between emission of stimulation pulses to the atrium andventricle is equal to the difference in time between the first andsecond interval and is referred to as the AV delay. It normallycorresponds to an interval lasting 100-200 milliseconds.

Normally, rate-modulating stimulation devices in current use determinethe rate for emitting stimulation pulses as a function of themeasurement value(s) for one or a plurality of parameters related to thephysical load to which a person is subjected. These measurement valuesare sensed by suitable sensors devised in different ways. One suchsensor can be an electrically powered flow meter, as shown in thepublished European patent application 0 634 192. In other instances, theimpedance of a heart ventricle is determined and, accordingly, strokevolume. Electrical impedance is measured between a stimulation electrodein a ventricle and some other electrode in the body or, especially. theheart, as is the case in U.S. Pat. No. 5,417,715 which is included as areference.

In certain embodiments, e.g. as described in the aforementioned U.S.patent, only the ongoing heart cycle is reviewed, and an appropriatetime for the generating of a stimulation pulse is mainly determined frommeasurement values previously obtained in the same cycle, whereasmeasurements in previously proposed embodiments are made over aplurality of heart cycles which, in certain instances, may bewell-separated in time. In principle, as is also discussed in theaforementioned U.S. patent, a well-selected or advantageous time forstimulating a heart is deemed to be when there is sufficient blood in aventricle for it to be pumped out of same. Such a stimulation largelyresembles the one which occurs naturally in a healthy heart. So aneffort should be made to select a heart rate enabling these times to beachieved or at least times which are not too far removed from them.Heart stimulator designs supplying such times are previously knownthrough e.g. the aforementioned U.S. patent and are discussed below.

The European patent EP-B1 0 551 355 shows how the interval elapsingbetween two consecutive stimulation pulses is continuously varied orreset with the aid of measurement of a parameter for the heart'sactivity. The parameter is measured as related to a single change in theduration of the stimulated heart cycle compared to the measurement valuefor the preceding heart cycle. The individual changes, only made formeasurement purposes, are performed with intervals between them which donot affect general pressure in the circulatory system. The parameter isimpedance between e.g. an electrode placed in the heart and a pacemakerhousing, and this impedance represents, or is related to, the heart sstroke volume. The ratio is formed between impedance changes, withchanges of equal but opposite magnitude, in the interval betweenstimulation pulses, and this value is compared to a reference valuewhich can be constant or dependent on heart rate. When hemodynamic rateoptimization is proposed, the time elapsing between two stimulationpulses is reduced on individual occasions until the change in impedancestops increasing. a procedure supplying a measure of the stroke volume.Here, it must be assumed that normal stimulation is too slow andutilizes a sub-optimal stimulation rate, which should be the result witha rate corresponding to the interval used when the change in impedancestops increasing.

U.S. Pat. No. 5,156,147 shows an adaptive pacemaker in which the changein the heart's pumped volume per unit of time, i.e. cardiac output (CO).is determined when heart rate increases. If the change is negative, i.e.reduced cardiac output then results, the increase in heart rate iscanceled. It also notes that the increase in one possible embodiment canbe also canceled if the increase in heart rate causes a drop in theincrease rate for cardiac output.

SUMMARY OF THE INVENTION

An object of the invention is to provide a device which simply andeffectively controls the emission of stimulation pulses at a rate orwith a rhythm selected so the function of a heart receiving these pulsessimulates, to a great degree, the function of a normally working heart,thereby preventing the imposition of needlessly heavy strain on heartmuscle at any given load.

Another object of the invention is to provide a device for deliveringstimulation pulses to a person s heart at a rate or rhythm which isautomatically adjusted to the work load sustained by the person.

Thus, the problem the present invention will solve is to provide astimulation devices which determines, in a safe and effective fashion,optimal times for the generating of stimulation pulses through the useof reliable and, preferably, simple algorithms. The times for pulseemission must also be constantly adapted to a person's prevailingphysical work load.

It is assumed, in the same way as in the aforesaid U.S. Pat. No.5,417,715, that the time at which a stimulation pulse is to be generatedis selected in such a way that optimal filling of a heart ventricle isachieved in each cardiac cycle. Thus, the slowest possible heart rate isthereby used for each load situation, i.e. the amount of blood requiredper unit of time to accommodate the physical work load, thereby imposinglight strain on heart muscle. In determinations of this time and thecorresponding heart rate and stimulation interval, in which thestimulation interval is the time elapsing between consecutivestimulation pulses, the stimulation interval is varied around the valueselected for the moment in a wav similar to the procedure described inthe aforesaid patents European Patents 0 551 355 and U.S. Pat. No.5,156,147, and a measure of the degree of filling is determined as afunction of heart rate.

Heart cycle durations corresponding to a plurality of different heartrates are used, then supplying measurement values for the correspondingdegree of filling.

In order to achieve simple and reliable determination of the optimalinterval, an appropriate mathematical function of both heart rate and adegree of filling is selected which achieves an extreme point, e.g. apeak value, at the optimal heart rate. Such a design could also simplifyand improve the efficiency of control and calculation circuits in thestimulation device. A heart rate is selected which supplies the functionan extreme value, a peak value in particular, and it is subsequentlyused as a new optimal heart rate. One preferred mathematical function isthe arithmetic product of heart rate and stroke volume raised to thesecond power.

According to the aforesaid U.S. Pat. No. 5,156,147, a mathematicalfunction, cardiac output, which is the arithmetic product of heart rateand stroke volume, is used in determining the optimal heart rate. Inthis function the heart rate is determined at which the functiondisplays a knee, i.e. changes from an essentially constant progressionto a declining progression. A knee obtained at the intersection of twostraight lines or curves is easily defined, of course, since it is foundat the intersection between the lines and curves respectively. Forfunctions obtained or measured in physical processes and which develop aknee in some area, the knee generally consists of a gentle transitionbetween e.g. two mainly straight lines. It is then mathematicallydifficult to define, unequivocally, the point in the gentle transitionat which the knee is located or should be located. One suchdetermination of the location of a knee in a function in a physicallydetermined function will then be much more difficult and unreliable thandetermination of e.g. a peak value for a physical function.Determination of a knee also requires more complex algorithms, which cancontain different logical choices or comparisons and are, therefore,non-standard, which must be processed by the electronic calculationcircuits in the stimulation device, increasing, in turn, circuitcomplexity. Increased circuit complexity can, in turn. increase thecircuits' power consumption.

The electrical impedance measured between an electrode placed in a heartventricle and another electrode, which can be placed inside or outsidethe heart, is related to the amount of blood in a heart ventricle. Inparticular, impedance can be determined when it reaches a peak value,which occurs when the heart ventricle contains a minimum amount ofblood. Impedance can further be determined in the same heart cycleimmediately before blood is ejected out of the ventricle when the nadirvalue for impedance is achieved, i.e. in practice immediately before theemission of a stimulation pulse, e.g. a pulse for stimulating an atrialcontraction. The difference between impedance values measured in thesame heart cycle constitutes a relative measure of stroke volume, sothis difference, within certain limits, can be regarded as a strictlydeclining function of stroke volume, thereby resulting in a one-to-oneratio between the value for impedance and the value for stroke volume.Instead of a function of heart rate and stroke volume, a correspondingfunction of heart rate and the impedance difference can be used whichhas extreme values for the same values for heart rate. Thus, a functioncan be used which is the product of heart rate and the impedancedifference raised to the second power.

When an appropriate sign is selected, the chosen function can always bemade to have a peak at a given heart rate, henceforth referred to as"the optimal heart rate". The heart rate supplying this peak value canbe determined in different ways.

One simple method is to have the pacemaker stimulate at a fixed rate andassign occasional intervals a length which deviates from the length ofintervals in the fixed rate. Some kind of determination of stroke volumeis performed, at least for the heart cycle with an altered duration,e.g. impedance is measured, and the value of the selected function canbe calculated. This value for the function is compared to acorresponding value for a function calculated in the immediatelypreceding determination. If the new functional value proves to belarger, the interval used for determining that value is closer the heartcycle duration corresponding to the optimal heart rate. The intervalwith the altered duration is then used thereafter, and the fixed heartrate is changed to correspond to a heart cycle employing the interval'slength. Otherwise, the interval used in the fixed heart rate temporarilyset is closer to the heart cycle duration employing the optimal rhythm.No change in the fixed heart rate set then needs to be made.

However, it is not known in either instance whether the selected heartrate is optimal, so an individual interval is again assigned a differingduration. The duration of this interval can be selected e.g. so thechange in relation to the prevailing fixed heart is in the oppositedirection to the change resulting in a lower functional value in thepreceding determination using a test interval with a deviating duration.In a somewhat different procedure, the difference between the durationof the new interval set and the duration of the interval correspondingto the prevailing fixed rate is assigned an arithmetic sign opposite tothe sign for the immediately preceding test interval in instances inwhich no change was made in heart rate. In instances in which a changeis made, the sign for the difference can be set at the same sign as forthe difference calculated for the preceding test interval. These changesin the duration of individual heart cycles are made until twoconsecutive functional values have been calculated which fail to produceany change in the prevailing fixed rate. The prevailing fixed rate isthen as close to the optimal value as can be determined with thisstepping method.

In instances in which functional values for two consecutive testintervals are identical, it can be assumed that the optimal ratecorresponds to a heart cycle duration between the durations of thesetest intervals. The optimal rate can then be set at a valuecorresponding to e.g. one heart cycle duration which is the mean valueof the duration of these test intervals.

If other anomalies are present in measurement values, such as theformation of plateaus in the morphology of the selected function, thissimple procedure could lead to unreliable optimization of the heartrate. In order to reduce errors caused by measurement data. measurementvalues, determined for more than two intervals with different durationsand weighting of the functional values calculated from these measurementvalues, are preferably used for determining an optimal heart rate. Thus,a measurement procedure can be used entailing variation in heart cycles,chronologically separated from each other, in which the prevailing heartrate generally employed is varied in the same wav as in the aforesaidEuropean patent 0 551 355. The values for the selected functions arecalculated for the various heart cycles set, especially for heart cycleswith deviating lengths, and the heart cycle duration producing peakfunctional performance is determined from these functional values. Thesimplest way to perform a determination is to take the heart cycleduration, and associated heart rate supplying the peak value, and usingthis rate as the new heart rate. A more accurate and reliabledetermination can be made by approximating the calculated values with asimple function, e.g. a second degree function such as a parabola, andcalculating the corresponding heart cycle duration from the peak valueof the approximated function which is thereupon utilized in stimulatingthe heart.

However, this procedure can be needlessly complex and result inexcessively long regulation times. Since rapid adaptation of heart rateto new and changed physiological requirements is sometimes necessary, amore appropriate procedure might be to conduct continuous searches sothe duration of each stimulation interval differs from the duration ofthe preceding interval. Changes from the optimal heart cycle durationshould then differ so little that there is no perceptible change inaverage blood pumping capacity while still being as large as possible toenhance accuracy in determination of stroke volume and, in particular,in determination of differences in impedance. A new optimal heart rateis calculated for each heart beat from the most recently calculatedfunctional values. Alternately, a new optimal heart rate can becalculated after every series of a number of consecutive heart cycleswith varying durations, the number being greater than two, e.g. four,calculations only being based on functional values determined for theheart cycles in this series. In one preferred embodiment, therefore,impedance measurements can be made for a plurality of consecutive heartcycles whose duration is varied from a heart cycle duration assumed tobe the best at the moment and corresponding to the optimal heart rate asabove. The heart cycle duration therefore is changed for each new cycle,and this should be performed so the average interval between stimulationpulses is essentially the same as the calculated optimal duration at themoment or equal to a reference value for duration, at least for theintervals between several consecutive stimulation pulses. The durationof intervals between stimulation pulses should also deviate in analternating fashion from the reference value so the duration of everyother interval exceeds the reference value, and the duration of everyother interval is less than the reference value.

In these methods with continuous searches the optimal heart rate,corresponding to the reference value for stimulation intervals, isconstantly adjusted. Stimulation is not performed exactly so thereference value is obtained for the next heart cycle and stimulationinterval but with an appropriately selected deviation so a possible newreference value can speedily and reliably be found. An additionalimprovement in the determination of the optimal heart rate can beachieved when calculations allow a new reference value to relate to theimmediately preceding reference values, e.g. so no changes are madewhich are too fast and/or too large, with the aid of recursive low passfiltration of the reference values.

In the embodiments discussed above, only a few current values arecompared, and no absolute reference is needed for the measured signal.The impedance measurement therefore only needs to be stable for arelatively brief period of time. However, Impedance measurement mustdisplay good sensitivity.

DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph showing a curve of a physiological variable, and twoderived curves as a function of heart rate, for use in accordance withthe present invention.

FIG. 2 schematically illustrates a pacemaker connected to a heart forventricular stimulation.

FIG. 3 is a block diagram of a stimulation device constructed andoperating in accordance with the principles of the present invention.

FIG. 4a is a typical electric cardiogram.

FIG. 4b is a graph showing how impedance measured across a heartvariable, varies as a function of time, with the same scale as theelectric cardiogram of FIG. 4a, this variation being used in accordancewith the principles of the present invention.

FIGS. 5a-5c are flowcharts showing steps performed in a micro-processorwithin a heart cycle employing different inventive algorithms.

FIG. 6 is a flowchart for determining the rate value corresponding to apeak value of the auxiliary function calculated from measurement valuesin accordance with the invention.

FIG. 7 is a graph showing the auxiliary function HF calculated inaccordance with the invention, relative to the stimulation interval T.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

FIG. 1 shows different units characteristic of a heart's pumping ofblood as a function of the heart's rhythm or rate. The solid line SVdesignates the heart's stroke volume, i.e. the amount of blood pumped bya heart ventricle in one heart cycle. When the heart rate is slow,stroke volume is directly related to the heart ventricle's maximumblood-filled volume before the ventricle contracts to eject blood. AsFIG. 1 shows, stroke volume in the depicted area displays relativelyconstant progression as heart rate increases, but the curve starts auniform, linear descent from a breakpoint. The descending curveindicates that the heart ventricle did not have enough time to fillcompletely with blood at fast rates. The curve CO designates the volumeof blood ejected per unit of time, i.e. cardiac output, and is theproduct of stroke volume SV times heart rate HR. The curve CO displayscorresponding progression with a breakpoint at the same value for heartrate. So this curve is generally linear up to the breakpoint, thereafterdisplaying an essentially constant morphology. The optimal rate at whichthe heart should preferably be stimulated in order to achieve theslowest possible heart rate, commensurate with accommodation of theexternal physical work load and supplying the lungs or circulatorysystem with the requisite flow of blood, lies somewhere near thebreakpoint.

The location of the breakpoint can be adaptively determined, as shown inU.S. Pat. No. 5,156,147. by increasing and reducing heart rate in stepsand determining whether cardiac 5 output increases or remains constant.However, indicating a criterion for e.g. the condition that the curve COmust be essentially constant is difficult. Another overlooked difficultyis to clearly define a breakpoint on a curve in the area in which thereis a smooth transition between two curve segments with differingmorphologies. So it would be desirable if an extreme point, such as apeak for a suitable function, could be sought instead. In principle, apeak can generally be determined in simple comparisons and is mucheasier to determine than the said breakpoint between a linear, rising orfalling segment and a segment with constant progression. Variouspossible, new functions can be derived from the general progression ofthe functions shown in FIG. 1. Thus, suitable linear functions can besubtracted from the curves SV and CO. Another possibility is to formsome suitable product from factors containing HR and SV in which thesecould be e.g. powers. One such curve HF is shown with the dashed line inFIG. 1 and was derived from the relationship HF=HR·SV² =SV·CO, i.e. itis a product of the curves shown with solid lines in FIG. 1.

Determination of maxima according to the above can be performed in aheart stimulator 1 (see FIG. 2 in which its connections to a heart areschematically depicted.). The stimulator or pacemaker 1 is connected byelectrical leads 3 and 5 to an end electrode 7 and a ring electrode 9connected to a heart. The stimulator 1 emits and delivers stimulationpulses to the heart across the electrodes 7, 9.

The internal structure of the stimulation device 1 is shown in theoverview block diagram in FIG. 3. An impedance measurement circuit 11,connected to the electrode leads 3 and 5, is used for determining theamount of blood in the heart ventricle and, accordingly, stroke volume.At intervals determined by a microprocessor 13, it emits an e.g. 4 kHzalternating current low-amperage signal with a brief duration. Duringthis time, electrical impedance, i.e. electrical current in relation tothe applied voltage signal, is measured. The microprocessor 13 receivesthe measured impedance value from the impedance measurement circuit foradditional processing. Alternately, impedance can be measured between anelectrode in the heart ventricle and an electrode located outside theheart, such as the metal enclosure which conventionally houses thestimulation device.

The microprocessor 13 is further connected to a read-only memory 15,ROM. and a read/write memory 17, RAM. It sends information to electroniccircuits 19, for emitting stimulation pulses, containing various controlcircuits for e.g. detecting electrical events in the heart whichdesignate atrial or ventricular contractions.

With the described construction, the microprocessor 13 is able tomeasure electrical impedance at appropriate times in order to obtain ameasure of the of ventricular filling. Measuring impedance Z₁ (see FIG.4a discussed below) can be appropriate at the time at which impedancereaches a peak value, and the heart ventricle has been emptied. Thisoccurs at an approximately fixed time about 250 to 300 millisecondsafter the stimulation pulse (cf. FIG. 4b and the discussion below). Theimpedance Z₂ can be further measured immediately prior to emission of astimulation pulse. The difference ΔZ=Z₁ -Z₂ between measurement valuesprovides a measure of stroke volume. A function HF_(Z) suitable formaximization can be calculated from HF_(Z) =(Z₁ -Z_(Z) ₂)HR. Andaccording to the above, it is approximately proportional to HF and hasthe same extreme values. An additional impedance measurement could alsobe made, in which case it is made between the described measurements ata fixed interval after the stimulation point, the interval beingconsiderably longer than the first. A more complicated expression for asuitable function is then obtained for use in optimization.

In subsequent determination of the heart rate or correspondingstimulation interval supplying the aforesaid peak value, the timeelapsing between two stimulation pulses is varied for a plurality ofconsecutive heart cycles, i.e. cycle duration is varied. The impedancedifference according to the above is determined for these cycles so thedifferences form a function of the stimulation interval or,equivalently, heart rate. As shown in the diagram in FIG. 7, thefunction can be determined for e.g. four different stimulationintervals, designated T_(i-3), T_(i-2), T_(i-1), T_(i). The impedancedifference for the stimulation interval T_(opt) deemed to be optimal forthe moment can obviously also be easily calculated and used, even ifthis is unnecessary. The changed stimulation intervals can e.g. beselected to lie symmetrically in pairs around the optimal stimulationinterval, such as T_(i-3) =T_(opt) +ΔT, T_(i-2) =T_(opt) -ΔT, T=T_(i-1)=T_(opt) +2·ΔT, T₁ =T_(opt) -2·ΔT, in which ΔT is a suitablv smallincrease in the stimulation interval. As a rule, such variations incycle durations do not cause the patient much discomfort or disruptcardiac function, provided variation values are small. A maximumvariation in cycle duration, corresponding to a rate change of ±5 heartbeats a minute, is therefore permissible in many cases. δT in theexample above would then correspond to a rate change of 2.5 beats aminute. Another paired, symmetrical distribution of measurement pointsaround T_(opt) yielding a uniform distribution is provided by T_(i-3)=T_(opt) +ΔT, T_(i-2) =T_(opt) -ΔT, T_(i-1) =T_(opt) ÷3·ΔT, T₁ =T_(opt)-3·ΔT. In this instance. δT corresponds to a rate change of 5/3=1.67heart beats/minute. The deviations in these examples are such thatpositive and negative deviations occur alternately, and deviation with apositive sign is followed by deviation of the same magnitude but with aminus sign, whereby each pair of deviations acquires a mean value equalto the optimal stimulation interval. The mean value of the deviationsfollowing a change in the optimal stimulation interval will also beequal to the optimal stimulation interval until the next change in theoptimal stimulation interval.

An alternative to this procedure is to measure only the difference inimpedance at a single change in the duration of the stimulation intervaland then to use only e.g. the four or five latest difference values indetermining the function's maximum HF so more "continuous"determinations are made. However, this can require a rather complexchoices for the duration of the changed stimulation interval.

Alternately, e.g. in cases in which such successive changes in theduration of the heart cycle would be too uncomfortable to the patient,the procedure according to the aforesaid European patent 0 551 335 canbe used. In this procedure, the interval between two stimulation pulsesduring individual, non-consecutive heart cycles, separated by aplurality of heart cycles with a regular stimulation interval deemed tobe optimal at the time, can be varied.

The value of the function HF according to the above can be calculatedfrom the impedance differences and associated values for the duration ofstimulation intervals. According to one simple procedure, a new, optimalstimulation interval T_(opt) yielding the largest value for the functionHF can be selected from the values for which impedance measurements weremade.

Alternately, a curve fitting method can be used for determining a pointat which HF has a maximum value. A suitable function is selected whichdisplays a reasonable simple progression, whose fitting to measured HFvalues can be expected (cf. FIG. 1). i.e. the peak of the dashed curve.One such function which can be easily calculated and used is a seconddegree function, i.e. a parabola. HF_(z),par =A·(T-T_(opt),new)₂ +B, inwhich A, B. T_(opt),new are constants determined during fitting, andT_(opt),new directly designates the stimulation interval value for whichthis function has a maximum. The second degree function can also bewritten HF_(z),par =a+bT₀ +cT₀ ² in which a, b, c are constants. See thediscussion of FIG. 6 below. If only three measurement values are used indetermining the maximum, the constants can be calculated by solving alinear equation system with three unknowns. If a number of measurementvalues are to be taken into account in the determination, the constantsare determined with the aid of some kind of regression analysis. Forexample, recursive adjustment of the constants can be made until theabsolute error between the measurement values and the function fallsbelow a predefined value.

The aforementioned determination methods are discussed in detail belowin conjunction with comments on FIGS. 4a and 4b and the flow charts inFIGS. 5a-5c. FIG. 4a shows a diagram of electrical voltage at points onthe body, located on opposite sides of the heart, for a heart stimulatedby a pacemaker. One such voltage curve is called a surfaceelectrocardiogram, and its general morphology was discussed above. The Pand T waves appear as small positive pulses, whereas the QRS complex ischaracterized by a large negative pulse. The stimulation pulses arevisible in the FIG. as negative, i.e. downward pointing, spikes for bothatrial and ventricular stimulation, a spike appearing immediately beforethe P wave and immediately before the QRS complex. This means that thedevice according to FIG. 2 must be augmented with an atrial electrode,an associated electrical lead and control and drive circuits. Cf. U.S.Pat. No. 5,417,715 (FIG. 6) cited above. However, the stimulation pulsesreferred to below are only ventricular stimulation pulses. The pacemaker1 is unable to generate a surface electrocardiogram according to FIG. 4abut can only pick up electrical voltage between points inside the body,said voltage displaying a somewhat different chronological progression.Cf, the discussion above. For example, the voltage between the endelectrode 7 and the metallic surface of an enclosure housing thestimulation device 1 can be picked up and used by the stimulation devicefor detecting atrial and ventricular events in the known fashion.Alternately, voltage can be determined between the end electrode 7 andthe ring electrode 9.

The diagram in FIG. 4b shows electrical impedance, measured e.g. betweenthe end electrode 7 and the ring electrode 9, as a function of time forthe heart for which the electrocardiogram in FIG. 4A was recorded.According to the above, the impedance is a function of the degree ofheart ventricle filling and has an area comprising its largest valuesimmediately before and/or around the T wave when the heart ventricle canbe assumed to be as empty of blood as possible. The lowest values arefound in the area immediately before and/or at the start of the QRScomplex, corresponding to maximal filling of the heart ventricle.

The sequence of different steps performed by the microprocessor 13 willnow be described, referring to the flowchart in FIG. 5a, for a firstconceivable embodiment, entailing a simple search for a maximum. Themethod starts from starting block 501, and T_(opt) is subsequentlyinitiated in a block 503 at an appropriately selected value T_(start).Moreover, a variable ΔT is assigned a starting value ΔT_(start). Thisvariable ΔT can have both a positive and negative value and designatesthe time shift in the interval T_(opt) used for stimulation to be usedfor the next impedance measurement when the interval T_(opt) is changedfor a single heart cycle to T_(opt) +ΔT. A suitable time tSt,, isfurther determined at which the first stimulation pulse is to beGenerated. In the next block 505. stimulation pulses are Generated atthe times t_(stim) =t_(start) +i·T_(opt) in which i runs through theintegers 0, 1, 2 . . . , n, n being a suitably selected whole number,n≧0 in which n can advantageously have a value greater than 1.

When these stimulation pulses have been Generated, an impedancemeasurement is performed in the next heart cycle, and the next heartcycle's interval is set in block 507 at T₀ =T_(opt) +ΔT. Impedance Z₁ ismeasured in block 509 after a given fixed delay D, on the order of250-300 ms. after the last stimulation pulse. The delay D is selected sothe heart ventricle in this impedance measurement is as empty of bloodas possible. i.e. measurement is made when the value for impedance isabout maximal. See FIG. 4b. The time at which measurement is made isthen t₁ =t_(start) +n·T_(opt) +D. An additional impedance measurement isthen made in the next block 51 1 with the measured impedance Z₂ in thesame heart cycle, immediately before (i.e., by a small positive time δT)the next stimulation pulse and, thus, at the time t₂ =t_(start)+n·T_(opt) +T₀ -δT=t_(start) +(n+1)·T_(opt) +ΔT-δT. The stimulationpulse is then emitted at the time t_(stim) =t_(start) +(n+1)·T_(opt)+ΔT. In the block 513, a value for the function HF_(z) is calculatedfrom the relationship HF_(z) =(Z₁ -Z₂)² /T₀ =ΔZ² /T₀. The inverted valueof the duration T₀ of an heart cycle interval corresponds to the heartrhythm. The value for HF_(Z) is stored, with the current T₀ value, inRAM memory 17. See FIG. 3.

A determination is then made in block 515 as to whether two such valuesfor HF, are stored for different T₀ values. If this is not the case, theblock 517 is executed, whereupon the starting value t_(start) for thenext stimulation pulses emitted is set at t_(start) =t_(start)+(n+1)·T_(opt) +T₀. The arithmetic sign for the time delay value ΔT,i.e. a positive interval shift, is set at a negative value of the sameabsolute magnitude and vice-versa, is then changed in a block 19, andblock 505 is repeated. If block 515 found that two HF_(z) values werestored, block 521 is performed instead. These stored values are comparedto each other in this block, and if the most recently stored value issmaller than the immediately preceding stored value, there is no needfor any change in the optimal rate, and block 517 is again executed asabove. Otherwise, i.e. if the latest functional value determined waslarger, a change will be made, and the new starting value T_(start) isfirst set in block 523 to t_(start) +n·T_(opt) +2·T₀. Cf block 517above. The change is made when the optimal interval T_(opt) is set at T₀in block 525. Since the change in the duration of the heart cycle inthis instance proved to yield a higher functional value, the samedeviation value ΔT can be used as before in the search for an optimalheart cycle duration. After block 525, the cycle is therefore repeated,beginning with block 505.

A search for an optimal heart rate by determination of a maximum basedon a plurality of values and using the general procedure described inthe European patent EP-B1 0 551 355 cited above is shown in theflowchart in FIG. 5b. In principle, the procedure utilizes the samefirst steps 501'-513' as in the steps 501-513 described for FIG. 5aabove. However, values for the parameters can differ, so ΔT can differ,and n is always ≧1. But the block 515' is different, and determinationsare made in it as to whether four values for HF_(z) are stored fordifferent T₀ values. If this is not the case, block 517', which is thesame as block 517 in FIG. 5a, is executed. A new value for the timedelay ΔT is then selected in block 519' in some suitable manner, e.g. asdiscussed above and block 505' is executed once again. If block 515'found four HF_(z) values stored, block 521' is executed. This blockutilizes the stored functional values for determining the valueT_(opt),new for the heart cycle duration yielding a maximum value forHF_(z). A simple algorithm for this will be described below inconjunction with comments on FIG. 6. The determined value T_(opt),newwill henceforth be used. To this end, the new starting value t_(start)is first set at t_(start) +(n+1)·T_(opt) +T₀ +T_(opt),new in block 523'.Finally, the interval duration T_(opt) is set at T_(opt),new in block515. Block 519' is then executed as above with a new value for timedeviation ΔT, whereupon the entire process is repeated starting at block505.

The procedural steps performed in an embodiment with more continuousadaptation of heart rate are shown in the flow chart in FIG. 5c. Theprocedure starts from a starting block 501", and parameter and startingvalues are then set in block 503". An optimal stimulation intervalT_(opt) is set at an appropriate starting value T_(start). Moreover,time deviation ΔT is assigned an appropriate positive starting value.Moreover, an appropriate time t_(start) is determined at which the firststimulation pulse is to be Generated. Moreover, values are determinedfor the coefficients k₁, k₂ . . . , k_(m) which are used with the fixedtime deviation ΔT to form different time deviations. See below! Typicalvalues can be m=4 and k₁ =1, k₂ =-1, k₃ =2, K₄ =-2 or k₁ =1, k₂ -1, k₃=3, k₄ 32 -3. A stimulation pulse is Generated in the next block 505 attime t_(stim) =t_(start).

A counter n in the next block 506" is assigned an initial value equal toone, and the heart cycle's next interval is then set at T₀ =T_(opt)+K_(n) ·ΔT in block 507", i.e. it is assigned a duration which differsby k_(n) ·ΔT from the optimal duration T_(opt) which is a referencevalue for the heart cycle and which is not directly used as a durationfor an actual heart cycle. In the subsequent blocks 509"-513", the sametasks are performed as in blocks 509-513 in FIG. 5a. A query as towhether a sufficient number of new functional values are stored is thenmade in block 515". This is performed by comparing the counter value nwith the fixed quantity m set. If this is not the case, the counter n isincremented one step in block 517", and block 507", which was describedabove, is executed to permit determination of additional functionalvalues. If block 515" determines that the counter n has reached itsfinal value, block 521" is performed. Block 521", like block 521' inFIG. 5b, compares stored functional values m to each other fordetermining the value T_(opt) for the heart cycle duration yielding amaximum value for HF_(z). Cf. FIG. 6. After this, a new determination ofan optimal heart cycle duration is made, and the procedure switches tothe above-described step 506" with initiation of the counter n,whereupon the determination loop 507"-519" is repeated m number oftimes.

It is obvious that the described procedures will only work with timesbetween consecutive stimulation pulses, and no absolute times t_(stim),s_(start) need to be used. The time delays ΔT can be stated either asabsolute values or expressed as a current stimulation duration T_(opt).For example, the values ΔT=+2.5%, -2.5%+5%, -5% of T_(opt) could be usedin block 519' in FIG. 5b.

FIG. 6 shows a block diagram for a sub-routine which can be used fordetermining the value for heart cycle duration T₀ yielding a maximumvalue for HF_(z). CF, blocks 521' and 521" in FIG. 5b and 5crespectively!. The routine starts in block 601, whereupon the maximumand minimum values for HF_(z) in the four stored values are determined.They are designated HF_(z),max and HF_(z),min. A determination issubsequently made in block 605 as to whether the variation in HF_(z)values is small, i.e. is less than a selected small value δ. If this isthe case, the interval value used is acceptable, so T_(opt),new is setat T_(opt) in block 607. After this, the routine concludes in end block609. If block 605 determined that variation exceeds the value δ, a block611 determines whether the largest value for HF_(z), i.e. HF_(z),max,corresponds to the smallest value for T₀. If this is the case, the newinterval T_(opt),new, is set at this value in block 613. The routinethen terminates again in block 609. If the determination in block 611was negative, i.e. found that the largest value for HF_(z) was notobtained at the smallest T₀, block 615 is performed instead. Here, aquery is made, in the corresponding manner, as to whether the largestvalue for HF_(z) is obtained at the highest T₀ value. If this is foundto be the case, the new interval is set in a block at this value, i.e.T_(opt),new. The routine again concludes in block 609.

If the query in block 615 resulted in a negative reply and a maximum wasnot obtained for either the largest or smallest T₀ value, a maximum mustbe obtained for a value between these T₀ values. A more demandingcalculation is then made in block 619. First, stored measurement valuesare approximated, as noted above, with a second degree function orparabola HF_(z),par =a+bT₀ +cT₀ ² in which a, b, c are constants whichmust be numerically determined, and the constant c must also satisfy thecondition c<0 so the parabola is a type with a maximum. The T₀ value isdetermined which yields this maximum, and the new interval, i.e.T_(opt),new, is set equal to -b/2c. The routine is then concluded inblock 609. After this, new determinations are made of functional valuesby varying cycle duration. Thus, the method can revert e.g. to the flowchart in FIG. 5b in order to perform block 523'. Although modificationsand changes may be suggested by those skilled in the art, it is theintention of the Inventors to embody within the patent warranted hereonall changes and modifications as reasonably and properly come within thescope of their contribution of the art.

What is claimed is:
 1. An implantable heart stimulation devicecomprising:a pulse generator which generates a series of stimulationpulses at a variable rate; an electrode connected to said pulsegenerator and adapted for delivering said stimulation pulses in vivo toa heart; a control unit connected to said pulse generator for causingsaid pulse generator to emit the respective stimulation pulses at settimes corresponding to respective at rates; a stroke volume at measuringunit for measuring respective stroke volumes of said heart at differentrates of said stimulation pulses; a calculation unit, connected to saidcontrol unit and to said stroke volume measurement unit, for calculatingvalues of an auxiliary function of two independent variables which, withthe stroke volumes from said stroke volume measurement unit and therates from said control unit as said two independent variables, producesa function of rate alone having an extreme point indicative of acalculated rate at which optimal heart functioning occurs; and anextreme point identifier, supplied with said values of said auxiliaryfunction, which identifies said calculated rate, and that which isconnected to said control unit and which supplies said calculated rateto said control unit, said control unit setting said times for emissionof respective stimulation pulses dependent on said calculated rate. 2.An implantable heart stimulation device as claimed in claim 1, whereinsaid calculation unit employs an auxiliary function having said extremepoint at a heart rate substantially at which a constant load andincreasing heart rate change from increasing values to decreasingvalues.
 3. A device as claimed in claim 1, wherein said calculation unitcalculates said auxiliary function as a product of said heart rateraised to a selected expediential power and said stroke volume raised toa selected expediential power.
 4. An implantable heart stimulationdevice as claimed in claim 3, wherein said selected expediential powerof said heart rate comprises the second power, and wherein said secondexpediential power of said stroke volume comprises the second power. 5.An implantable heart stimulation device as claimed in claim 1, whereinsaid stroke volume measurement unit comprises a pair of electrodesadapted for a invivo implantation in a heart for measuring electricalimpedance between said pair of electrodes.
 6. An implantable heartstimulation device as claimed in claim 1, wherein said control unitchanges an interval between successive stimulation pulses at selectedtime, differing from an interval between said times for emission of saidrespective stimulation pulses dependent on said calculating rate, andwherein said stroke volume measurement unit measures said stroke volumeat said selected times.
 7. An implantable heart stimulation device asclaimed in claim 1, wherein said control unit constantly changes aninterval between successive stimulation pulses from an intervalcorresponding to said times for emission of respective stimulationpulses dependent on said calculated rates, said control unit changingsaid interval with alternating signs and said stroke volume measurementunit determining said stroke volume for the changed intervals.
 8. Animplantable heart stimulation device as claimed in claim 1, wherein saidcontrol unit constantly changes an interval between successivestimulation pulses from said times for emission of respectivestimulation pulses dependent on said calculated rate to differentintervals, and wherein said stroke volume measures these stroke volumemeasures the stroke volume during said different intervals, said controlunit maintaining an average interval between said stimulation pulses asbeing substantially equal to said interval for said times for emissionof respective stimulation pulses dependent on said calculated rate.
 9. Adevice for emitting stimulation pulses at a variable rate to a heart,comprising:a pulse generator which generates a series of stimulationpulses at a variable rate; an electrode connected to said pulsegenerator and adapted for delivering said stimulation pulses in vivo toa heart; impedance measuring means for measuring a change in theimpedance in cardiac tissue during one heart cycle at times selected sothat said change in impedance is indicative of a stroke volume of saidheart during said one heart cycle; control means for changing aninterval between successive stimulation pulses from an interval valuecorresponding to a reference value, said change in the impedance beingobtained as a function of heart rate; calculation means connected tosaid impedance measuring means for determining stoke volume, andconnected to said control means, said calculation means calculating anauxiliary function from two independent variables selected so that whenthe heart rate and the change in impedance as a function of heart rateare used as said variables instead of auxiliary function, a function ofheart rate alone is obtained with an extreme point representing a heartrate value at which optimal cardiac function is achieved, saidcalculation means supplying said heart rate value to said control meansfor use as a new reference value.
 10. A device as claimed in claim 9,wherein said calculation means comprises means for determining the heartrate HR using an auxiliary function Hf_(z) =HR·ΔZ², wherein ΔZ is saidchange in impedance, and said control unit supplying said heart rate HRto said control means for use as said new reference value.